Studies on the pathogenesis of hypokalemia in Gitelman's syndrome: role of bicarbonaturia and hypomagnesemia.
OBJECTIVE
Hypokalemia and renal potassium (K) wasting are hallmarks of the group of disorders called Bartter's syndrome. The presence of hypomagnesemia and a low rate of excretion of calcium are currently used to characterize a subgroup of these patients as having Gitelman's syndrome (GS) in which the molecular lesion is a defect in the thiazide-sensitive NaCl cotransporter in the distal convoluted tubule. This study was undertaken to examine whether bicarbonaturia or hypomagnesemia exacerbates the kaliuresis in patients with GS.


METHODS
Six patients with most of the diagnostic features of GS were examined. To examine the role of bicarbonaturia, the transtubular K concentration gradient (TTKG) was assessed before and after an oral load of NH4Cl which caused the urine pH to be < 6. To evaluate the role of hypomagnesemia, the TTKG was examined after an infusion of enough magnesium (Mg) to achieve normal levels of Mg in plasma for close to 24 h.


RESULTS
The TTKG remained very high even when the pH of the urine was < 6.0. An infusion of Mg caused the TTKG to approach expected values for hypokalemia in 4 of 6 patients. The infusion of Mg was extended in 1 patient who had a sustained high TTKG for 24 h; the TTKG remained elevated for 96 h despite normal plasma Mg levels.


CONCLUSIONS
Bicarbonaturia does not play a critical role in maintaining the very high TTKG in these patients. The K wasting in 4 of 6 of these patients could largely be attributed to hypomagnesemia and/or Mg depletion. The plasma aldosterone level tended to be higher in patients who did not respond to the infusion of Mg. Therefore, these patients may not represent a homogeneous group with regard to the pathophysiology of their renal K wasting.
Kamel
K S
KS
Department of Medicine, St. Michael's Hospital, Toronto, Ont., Canada.
Harvey
E
E
Douek
K
K
Parmar
M S
MS
Halperin
M L
ML
D000328:Adult; D000643:Ammonium Chloride / Q000494:pharmacology; D001477:Bartter Syndrome / Q000097:blood / Q000503:physiopathology* / Q000652:urine; D001639:Bicarbonates / Q000652:urine*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007008:Hypokalemia / Q000503:physiopathology*; D007684:Kidney Tubules / Q000503:physiopathology; D008274:Magnesium / Q000097:blood*; D008278:Magnesium Sulfate / Q000008:administration & dosage / Q000494:pharmacology; D008297:Male; D011188:Potassium / Q000378:metabolism; D013577:Syndrome
D001639:Bicarbonates; D000643:Ammonium Chloride; D008278:Magnesium Sulfate; D008274:Magnesium; D011188:Potassium